A biomechanical comparison of initial sprint acceleration performance and technique in an elite athlete with cerebral palsy and able-bodied sprinters

Cerebral palsy is known to generally limit range of motion and force producing capability during movement. It also limits sprint performance, but the exact mechanisms underpinning this are not well known. One elite male T36 multiple-Paralympic sprint medallist (T36) and 16 well-trained able-bodied (AB) sprinters each performed 5–6 maximal sprints from starting blocks. Whole-body kinematics (250 Hz) in the block phase and first two steps, and synchronised external forces (1,000 Hz) in the first stance phase after block exit were combined to quantify lower limb joint kinetics. Sprint performance (normalised average horizontal external power in the first stance after block exit) was lower in T36 compared to AB. T36 had lower extensor range of motion and peak extensor angular velocity at all lower limb joints in the first stance after block exit. Positive work produced at the knee and hip joints in the first stance was lower in T36 than AB, and the ratio of positive:negative ankle work produced was lower in T36 than AB. These novel results directly demonstrate the manner in which cerebral palsy limits performance in a competition-specific sprint acceleration movement, thereby improving understanding of the factors that may limit performance in elite sprinters with cerebral palsy

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

A biomechanical comparison of initial sprint acceleration performance and technique in an elite athlete with cerebral palsy and able-bodied sprinters

Cerebral palsy is known to generally limit range of motion and force producing capability during movement. It also limits sprint performance, but the exact mechanisms underpinning this are not well known. One elite male T36 multiple-Paralympic sprint medallist (T36) and 16 well-trained able-bodied (AB) sprinters each performed 5–6 maximal sprints from starting blocks. Whole-body kinematics (250 Hz) in the block phase and first two steps, and synchronised external forces (1,000 Hz) in the first stance phase after block exit were combined to quantify lower limb joint kinetics. Sprint performance (normalised average horizontal external power in the first stance after block exit) was lower in T36 compared to AB. T36 had lower extensor range of motion and peak extensor angular velocity at all lower limb joints in the first stance after block exit. Positive work produced at the knee and hip joints in the first stance was lower in T36 than AB, and the ratio of positive:negative ankle work produced was lower in T36 than AB. These novel results directly demonstrate the manner in which cerebral palsy limits performance in a competition-specific sprint acceleration movement, thereby improving understanding of the factors that may limit performance in elite sprinters with cerebral palsy.<br/

Coupling Postsynthetic High-Temperature Oxidative Thermolysis and Thermal Rearrangements in Isoreticular Zinc MOFs

Herein, we report coupling in situ high temperature postsynthetic modifications (PSMs) in metal–organic frameworks (MOFs). Thermo-reactive propargyloxy-functionalized zinc IRMOFs (isoreticular metal–organic frameworks) prepared from 2-(prop-2-yn-1-yloxy)-[1,1′-biphenyl]-4,4′-dicarboxylic acid (H2bpdcOCH2CCH) were investigated for their high-temperature postsynthetic rearrangement (PSR) chemistry to heterocyclic chromenes and benzofurans and then coupled to solid–gas reactions with molecular oxygen. The selectivity for the initial molecular rearrangements was found to be inverted in the porous MOF environment compared to conventional melt reactions of the ester compound Me2bpdcOCH2CCH and proceeded far more easily than the solid-state transformation from H2bpdcOCH2CCH, showing the potential of MOFs to give rise to different chemistry. The major oxidative process was thermolysis of the chromene ring with a minor pathway of allylic-type oxidation to give heterocyclic chromenone functionality. The sequence was also successful on a series of two-component multivariate IRMOF frameworks prepared from thermo-reactive H2bpdcOCH2CCH and thermo-resistant H2bpdcOMe linkers, demonstrating that these reactions can be used with known crystal engineering strategies. All transformations were fully compatible with the requirements to maintain MOF crystallinity and porosity as evidenced by surface area analysis and X-ray powder diffraction measurements. This work contributes to establishing the feasibility of high-temperature solid–gas manifolds for MOF PSM.</p

A biomechanical comparison of initial sprint acceleration performance and technique in an elite athlete with cerebral palsy and able-bodied sprinters

Cerebral palsy is known to generally limit range of motion and force producing capability during movement. It also limits sprint performance, but the exact mechanisms underpinning this are not well known. One elite male T36 multiple-Paralympic sprint medallist (T36) and 16 well-trained able-bodied (AB) sprinters each performed 5-6 maximal sprints from starting blocks. Whole body kinematics (250 Hz) in the block phase and first two steps, and synchronised external forces (1000 Hz) in the first stance phase after block exit were combined to quantify lower-limb joint kinetics. Sprint performance (normalised average horizontal external power in the first stance after block exit) was lower in T36 compared to AB. T36 had lower extensor range of motion and peak extensor angular velocity at all lower limb joints in the first stance after block exit. Positive work produced at the knee and hip joints in the first stance was lower in T36 than AB, and the ratio of positive:negative ankle work produced was lower in T36 than AB. These novel results directly demonstrate the manner in which cerebral palsy limits performance in a competition-specific sprint acceleration movement, thereby improving understanding of the factors that may limit performance in elite sprinters with cerebral palsy

Coupling Postsynthetic High-Temperature Oxidative Thermolysis and Thermal Rearrangements in Isoreticular Zinc MOFs

Herein, we report coupling in situ high temperature postsynthetic modifications (PSMs) in metal-organic frameworks (MOFs). Thermo-reactive propargyloxy-functionalized zinc IRMOFs (isoreticular metal-organic frameworks) prepared from 2-(prop-2-yn-1-yloxy)-[1,1′-biphenyl]-4,4′-dicarboxylic acid (H2bpdcOCH2CCH) were investigated for their high-temperature postsynthetic rearrangement (PSR) chemistry to heterocyclic chromenes and benzofurans and then coupled to solid-gas reactions with molecular oxygen. The selectivity for the initial molecular rearrangements was found to be inverted in the porous MOF environment compared to conventional melt reactions of the ester compound Me2bpdcOCH2CCH and proceeded far more easily than the solid-state transformation from H2bpdcOCH2CCH, showing the potential of MOFs to give rise to different chemistry. The major oxidative process was thermolysis of the chromene ring with a minor pathway of allylic-type oxidation to give heterocyclic chromenone functionality. The sequence was also successful on a series of two-component multivariate IRMOF frameworks prepared from thermo-reactive H2bpdcOCH2CCH and thermo-resistant H2bpdcOMe linkers, demonstrating that these reactions can be used with known crystal engineering strategies. All transformations were fully compatible with the requirements to maintain MOF crystallinity and porosity as evidenced by surface area analysis and X-ray powder diffraction measurements. This work contributes to establishing the feasibility of high-temperature solid-gas manifolds for MOF PSM